DNA replication, recombination and repair

BY PETER BAUMANN AND PATRICK SUNG

The three Rs – DNA replication, recombination and repair – are at the heart of proliferation, evolution and maintenance of genomes. Impairment of these processes results in genome instability and mutations that lead to cancer and other diseases. The four stimulating sessions in this year’s theme will focus on homology-directed repair of DNA damage, the interplay between replication and other fundamental cellular processes, and the special challenges associated with the maintenance and protection of chromosome ends.

DNA repair

The first session, “Mechanism and Regulation of DNA Repair,” focuses on various molecular aspects of the DNA homology-directed repair of damaged chromosomes.

Lorraine Symington (Columbia University) works with budding yeast to study the genetic mechanism of homologous recombination that is mediated by the RAD52 gene group and the involvement of recombination in DNA double-strand break repair, the maintenance of genetic stability and meiosis. She will discuss her recent work, which has shed light on the multifaceted role of several DNA helicases and nucleases in the early and late steps of the homologous recombination reaction.

Hiroshi Iwasaki(Tokyo Institute of Technology) will describe his biochemical reconstitution of homologous recombination reactions with recombinase proteins and their accessory factors from fission yeast. The detailed analyses of these reconstituted reactions have provided considerable insights into the mechanism and regulation of the early steps of homologous DNA repair and the resolution of DNA intermediates made by recombinase proteins.

Sua Myong (University of Illinois at Urbana-Champaign) has been at the forefront of applying single-molecule methodologies to examine the mechanism of action of DNA repair proteins and how the activities of DNA repair complexes are regulated. She will describe her recent work, which makes use of fluorescently labeled biomolecules and fluorescence cell imaging to define the mechanism of helicases and other enzymes involved in DNA repair and replication.

DNA replication

The second session, “DNA Replication Mechanism and Context,” highlights recent advances in our understanding of the assembly and regulation of replication complexes and explores the intricate interplay between replication and other nuclear processes.

John Diffley (Cancer Research UK) uses budding yeast and human cells to decipher the mechanism of DNA replication and its regulation at multiple levels. Biochemical reconstitution of initiation complexes has advanced significantly our understanding of replication origin choice, licensing and replisome assembly. He will discuss recent findings from his lab, including molecular studies that elucidate how checkpoints regulate origin firing.